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Introduction
Illustrated mechanism of action
Examples of Medication Brand Names (with Images)
Indication
Side Effects
Precautions & Contraindications
Monographs
Reference
Introduction
Atypical antipsychotics, also known as second-generation antipsychotics, are a group of medications primarily used to treat serious mental health conditions such as schizophrenia and bipolar disorder. Unlike first-generation (typical) antipsychotics, atypicals were developed to provide similar or better symptom relief while reducing certain side effects, especially movement-related issues (like tremors or stiffness).
These medications work mainly by affecting the dopamine and serotonin systems in the brain, helping to manage symptoms like hallucinations, delusions, mood swings, and irritability. In addition to their approved uses, they are sometimes prescribed off-label for conditions like depression, autism-related irritability, and anxiety disorders.
While they can be very effective, they also come with potential side effects, such as weight gain and metabolic changes, so their use requires careful medical supervision.
Illustrated mechanism of action
1. Dopamine D₂ receptor antagonism
• Atypical agents bind to postsynaptic D₂ receptors in the mesolimbic pathway and block dopamine’s ability to activate them.
• This “dopamine blockade” reduces positive symptoms of psychosis (hallucinations, delusions).
2. Serotonin 5-HT₂A receptor antagonism
• At the same time, these drugs block 5-HT₂A receptors on cortical and nigrostriatal neurons.
• By inhibiting serotonin’s suppression of dopamine release, they actually increase dopamine tone in areas where it’s needed (prefrontal cortex, nigrostriatal pathway).
3. Net result: fewer motor side effects
• In classic (typical) antipsychotics, strong D₂ blockade in the nigrostriatal pathway causes extrapyramidal symptoms (rigidity, tremor).
• Atypicals’ added 5-HT₂A antagonism “rescues” dopamine release there, so EPS are much less pronounced.
4. Improved negative and cognitive symptoms
• Enhanced dopamine in the prefrontal cortex (via 5-HT₂A blockade) can help with motivation, social withdrawal, and executive function.
1. Stahl, S. M. (2013). Stahl’s Essential Psychopharmacology: Neuroscientific Basis and Practical Applications (4th ed.). Cambridge University Press.
2. Meltzer, H. Y., & Massey, B. W. (2011). The role of serotonin in schizophrenia. Current Opinion in Pharmacology, 11(1), 59–65.
3. Kapur, S., & Mamo, D. (2003). Half‐life and “fast‐off” dissociation from the dopamine D₂ receptor: new insights into the mechanism of antipsychotic atypicality. American Journal of Psychiatry, 160(3), 420–429.
Examples of Medication Brand Names (with Images)
Seroquel ((Quetiapine))
Seroquel ((Quetiapine))
Risperdal (Risperidone)
Risperdal (Risperidone)
Geodon ((Ziprasidone))
Geodon ((Ziprasidone))
Indication
Indications of Atypical Antipsychotics
1. Schizophrenia
Treatment of acute and chronic schizophrenia in adults and adolescents.
2. Bipolar Disorder
Acute manic or mixed episodes (monotherapy or adjunct to mood stabilizers).
Bipolar depression (e.g., quetiapine, lurasidone, olanzapine/fluoxetine combo).
Maintenance treatment to prevent recurrence of mood episodes
3. Major Depressive Disorder (Adjunctive Therapy)
Adjunct to antidepressants in treatment-resistant depression (e.g., aripiprazole, quetiapine XR, brexpiprazole).
4. Autism Spectrum Disorder
Management of irritability, including aggression, self-injury, and severe tantrums (e.g., risperidone, aripiprazole).
5. Tourette's Syndrome
Management of tics and associated behavioral symptoms (e.g., aripiprazole).
6. Agitation Associated with Schizophrenia or Bipolar Mania
Short-term treatment of agitation in adults (e.g., intramuscular formulations of ziprasidone, olanzapine, aripiprazole).
7. Treatment-Resistant Schizophrenia
Specifically: Clozapine for patients unresponsive to other antipsychotics.
8. Suicidality in Schizophrenia or Schizoaffective DisorderClozapine is indicated to reduce the risk of recurrent suicidal behavior.
Side Effects
Atypical antipsychotics can cause a range of side effects, including:
Weight gain and metabolic disturbances such as increased risk of type 2 diabetes and high cholesterol.
Extrapyramidal symptoms (movement disorders) like tremor, restlessness, shuffling walk, and tardive dyskinesia, though these are generally less common than with typical antipsychotics.
Cardiovascular effects including QTc prolongation, changes in blood pressure, and potential increased risk of cardiovascular disease.
Antimuscarinic (anticholinergic) effects such as blurred vision, dry mouth, constipation (which can be severe), difficulty urinating, confusion, and rapid heartbeat.
Blood disorders including agranulocytosis (especially with clozapine), neutropenia, leukopenia, which increase infection risk and require regular blood monitoring.
Sedation, drowsiness, difficulty sleeping, and sexual dysfunction
Other possible effects include myocarditis, cataracts, pancreatitis, and rare but serious conditions like neuroleptic malignant syndrome.
Clozapine has a higher risk of serious side effects such as agranulocytosis and seizures, requiring careful monitoring.
Overall, atypical antipsychotics have fewer movement-related side effects than typical ones but carry significant risks related to metabolism, cardiovascular health, and blood cell counts
Precautions & Contraindications
Atypical antipsychotics can cause a range of side effects, including:
Atypical antipsychotics can cause a range of side effects, including:
Weight gain and metabolic disturbances such as increased risk of type 2 diabetes and high cholesterol.
Weight gain and metabolic disturbances such as increased risk of type 2 diabetes and high cholesterol.
Extrapyramidal symptoms (movement disorders) like tremor, restlessness, shuffling walk, and tardive dyskinesia, though these are generally less common than with typical antipsychotics.
Extrapyramidal symptoms (movement disorders) like tremor, restlessness, shuffling walk, and tardive dyskinesia, though these are generally less common than with typical antipsychotics.
Cardiovascular effects including QTc prolongation, changes in blood pressure, and potential increased risk of cardiovascular disease.
Cardiovascular effects including QTc prolongation, changes in blood pressure, and potential increased risk of cardiovascular disease.
Antimuscarinic (anticholinergic) effects such as blurred vision, dry mouth, constipation (which can be severe), difficulty urinating, confusion, and rapid heartbeat.
Antimuscarinic (anticholinergic) effects such as blurred vision, dry mouth, constipation (which can be severe), difficulty urinating, confusion, and rapid heartbeat.
Blood disorders including agranulocytosis (especially with clozapine), neutropenia, leukopenia, which increase infection risk and require regular blood monitoring.
Blood disorders including agranulocytosis (especially with clozapine), neutropenia, leukopenia, which increase infection risk and require regular blood monitoring.
Sedation, drowsiness, difficulty sleeping, and sexual dysfunction.
Sedation, drowsiness, difficulty sleeping, and sexual dysfunction.
Other possible effects include myocarditis, cataracts, pancreatitis, and rare but serious conditions like neuroleptic malignant syndrome.
Other possible effects include myocarditis, cataracts, pancreatitis, and rare but serious conditions like neuroleptic malignant syndrome.
Clozapine has a higher risk of serious side effects such as agranulocytosis and seizures, requiring careful monitoring.
Clozapine has a higher risk of serious side effects such as agranulocytosis and seizures, requiring careful monitoring.
Overall, atypical antipsychotics have fewer movement-related side effects than typical ones but carry significant risks related to metabolism, cardiovascular health, and blood cell counts
Overall, atypical antipsychotics have fewer movement-related side effects than typical ones but carry significant risks related to metabolism, cardiovascular health, and blood cell counts
Monographs
PH.SH.1165.docxph.sh.141.docxshahd elkady......docxDrug monograph (Clozapine) 3.docxDrug monograph (2)quetiapine.docxDOC-20250324-WA0041.........ssss.docxsamaa drug.docxReference
https://www.drugs.com/drug-class/atypical-antipsychotics.html?utm_source=perplexity
https://en.m.wikipedia.org/wiki/Atypical_antipsychotic?utm_source=perplexity
https://pmc.ncbi.nlm.nih.gov/articles/PMC2327229/?utm_source=perplexity
https://www.ncbi.nlm.nih.gov/books/NBK448156/?utm_source=perplexity
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